Background: Reactive oxygen species are usually produced by the living cell and have different functions in its normal activity and considered as one of the factors that involved in heart disease. Malondialdehyde (MDA) considered as one of the most indictors of oxidative stress and damage produced as a result of lipid peroxidation. Objectives: The main objective is to evaluate serum oxidative stress by measuring the changes in the level of MDA as a marker of oxidative stress and demonstrate the correlation of MDA with lipid profile in patients subjected to open-heart surgery. Methods: A case–control study was carried out in the Department of Chemistry and Biochemistry, College of medicine, Tikrit University, Tikrit, Iraq. The study was carried out for 50 patients subjected to open-heart surgery recruited from the Medical City/Iraqi Center for Heart Disease and Ibn Al-Bitar Cardiac Surgery Center, Department of Cardiac Surgery, Baghdad, Iraq between October 1, 2017 and March 1, 2018. The levels of MDA and lipid profile were measured in the serum of 50 patients, in three different interval preoperative, early postoperative, and late postoperative and compared with 30 age- and gender-matched controls. Results: The results revealed a statistically significant difference in the serum MDA level between patient during preoperative, early postoperative, and late postoperative stage against control group and significant differences in their MDA levels among all patients' stages. Furthermore, there was a significant positive correlation between serum MDA level and total cholesterol in the early postoperative stage. Conclusions: There was an increase in the level of MDA in the early postoperative stage as an indicator of reperfusion damage that occurs immediately after open-heart surgery which then decreases dramatically with decrease in total cholesterol, triglyceride, low-density lipoprotein-cholesterol (LDL-C), and very-LDL-C.